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ID PMID Title PublicationDate abstract
18381794 Methotrexate (MTX) pathway gene polymorphisms and their effects on MTX toxicity in Caucasi 2008 Apr OBJECTIVE: Research has examined the association of folate-dependent gene polymorphisms with methotrexate (MTX) toxicity in racially homogenous patients with rheumatoid arthritis (RA). We examined the influence of MTX transporter gene polymorphisms on MTX toxicity in 2 racial groups of patients with RA. METHODS: Using a retrospective cross-validation approach, the association of polymorphisms in 6 genes in the MTX cellular pathway with MTX toxicity was examined in training and validation cohorts. The genes analyzed were ATP-binding cassette transporter B1 (ABCB1), C1 (ABCC1), C2 (ABCC2), folylpolyglutamyl synthase (FPGS), methylenetetrahydrofolate reductase (MTHFR), and thymidylate synthase (TYMS). Both cohorts included Caucasian Americans and African Americans. Statistical analyses consisted of Fisher exact tests, multivariable logistic regression models, and survival analyses. RESULTS: Four of 25 variants displayed significant associations with MTX toxicity in the training cohort. The intronic single-nucleotide polymorphism (SNP) ABCC2 IVS 23+56 T --> C was associated with alopecia in Caucasians (p = 0.035). ABCB1 1236 C --> T was associated with overall toxicity (p = 0.013); ABCC2 1249 G --> A with gastrointestinal toxicity (p = 0.009); and ABCC2 1058 G --> A with hepatotoxicity (p = 0.04) in African Americans. These 4 SNP and the MTHFR 677 C --> T variant were assessed in the validation cohort. Of these, only the MTHFR 677 C --> T SNP was associated with alopecia, and only in African Americans (p = 0.032). The ABCC2 IVS 23+56 T --> C genotype influenced toxicity-related time to discontinuation or dose decrease in the Caucasian validation cohort (p < 0.0001). CONCLUSION: In addition to SNP in folate-dependent genes, MTX transporter gene SNP may be important markers of MTX toxicity in RA. Such pharmacogenetic associations are race-specific.
17565924 Abatacept: a novel therapy approved for the treatment of patients with rheumatoid arthriti 2007 Mar An enhanced understanding of the immunopathology of rheumatoid arthritis (RA) has led to the development of novel therapies that target specific events occurring in the immune cascade that underlies the disease. In December 2005, abatacept became the first therapy to be approved by the US Food and Drug Administration for the treatment of adult patients with moderately to severely active RA who have exhibited an inadequate response to traditional disease-modifying antirheumatic drugs or tumor necrosis factor antagonists. This article summarizes the characteristics and clinical profile of abatacept. Abatacept is a fully human soluble recombinant fusion protein that acts by binding to CD80/CD86 on antigen-presenting cells and inhibiting interaction with CD28 on T cells, thus preventing one of the co-stimulatory signals needed for full T-cell activation. It is indicated for reducing signs and symptoms of the disorder, inducing a major clinical response, slowing the progression of structural damage, and improving physical function in this patient population. Data on abatacept compiled to date demonstrate significant efficacy, combined with a consistent safety profile and tolerability, in a wide range of patients with RA, including those with an inadequate response to methotrexate or to tumor necrosis factor antagonists.
19027090 Anti-TNFalpha therapy in a cohort of rheumatoid arthritis patients: clinical outcomes. 2009 Jan OBJECTIVE: To assess the effectiveness of anti-TNFalpha agents by analysing the principal clinical outcomes in patients with active rheumatoid arthritis (RA). METHODS: 1010 patients who received no clinical benefit from previous treatment with methotrexate and/or other DMARDs, were subsequently treated with one or more of the anti-TNFalpha agents. RESULTS: After the first six months of anti-TNFalpha therapy, 29% of the patients showed a good and 47% a moderate European League Against Rheumatism (EULAR) response, and this positive result was maintained after two years of follow-up. Their median Disease Activity Score based on the erythrocyte sedimentation rate and the evaluation of 28 joints (DAS28) decreased from 5.94 at baseline to 4 after six months (p<0.001; Delta 1.94), and further significant responses were also observed after 12, 18 and 24 months; their median 36-month DAS28 score reflected mild disease activity. The median Health Assessment Questionnaire (HAQ) score fell from 1.34 at baseline to 1 after six months of therapy (Delta 0.34; p<0.05), and a further significant reduction was observed during the second and third year of follow up. CONCLUSIONS: Especially when combined with DMARDs, anti-TNFalpha drugs can induce a good clinical response regardless of the particular molecule used, whereas their combination with steroids does not seem to improve disease outcomes at any time during follow-up.
18612923 Circulating levels of osteopontin, osteoprotegerin, total soluble receptor activator of nu 2008 Jul OBJECTIVE: To determine whether circulating levels of osteopontin (OPN), osteoprotegerin (OPG), total soluble receptor activator of nuclear factor-kappa B ligand (total sRANKL), and high-sensitivity C-reactive protein (hsCRP) change in patients with rheumatoid arthritis (RA) during immunosuppressive therapy. METHODS: Twenty-five active RA patients were randomized to treatment with either etanercept alone or in combination with methotrexate (MTX). The treatment response after 16 weeks was assessed using the European League Against Rheumatism (EULAR) response criteria. Blood samples were taken before the start of and every fourth week during the study. OPN, OPG, and total sRANKL were measured by enzyme-linked immunosorbent assays (ELISAs) and hsCRP by highly sensitive turbidometry. RESULTS: At baseline, OPN and hsCRP were significantly (p<0.001) elevated compared to healthy persons. Compared to baseline only hsCRP levels decreased significantly (p<0.05 to p<0.001) in the EULAR responders through the study. OPN remained significantly (p<0.05) elevated at 16 weeks in patients with a low disease activity score (DAS< or =3.2). Total sRANKL increased significantly (p<0.05) from baseline to week 12. No statistically significant changes were observed in the non-responders. CONCLUSION: Active RA patients showed increased circulating levels of hsCRP and OPN, but only hsCRP decreased during etanercept therapy. Our findings suggest that OPN, OPG, total sRANKL, and hsCRP reflect different aspects of the inflammatory process in RA.
17392352 Double-blinded infliximab dose escalation in patients with rheumatoid arthritis. 2007 Sep OBJECTIVE: To determine the efficacy, safety and pharmacokinetics of infliximab dose escalation in patients with rheumatoid arthritis (RA) who had an inadequate response to 3 mg/kg infliximab treatment or whose disease flared after initially responding. METHODS: Patients with active RA, despite receiving methotrexate, received infliximab 3 mg/kg at weeks 0, 2, 6 and 14 in one of the three arms of the START trial. Beginning at week 22, patients had their infliximab dose increased in a double-blind fashion in increments of 1.5 mg/kg if the total tender and swollen joint count did not improve by at least 20% from baseline (lack of response) or the improvement at week 22 or later worsened by 50% or more (criterion for flare). RESULTS: Of the 329 evaluable patients, 100 (30.4%) patients required dose escalation at or after week 22 because of flare or lack of response. The majority of patients (>80%) who received up to three dose escalations showed >/=20% improvement in the total tender and swollen joint count after their last dose escalation. Patients who required dose escalations generally had lower preinfusion serum infliximab concentrations than those who did not require them. The incidences of adverse events and serious adverse events for the patients who received dose escalation(s) were similar to those of patients who did not receive dose escalation. CONCLUSION: Fewer than one-third of patients required a dose escalation. The majority of patients showed improvement after receiving increased doses of infliximab, without an increased risk of adverse events.
16905577 Differential effect of methotrexate on the increased CCR2 density on circulating CD4 T lym 2007 Feb OBJECTIVES: To evaluate the effect of orally administered methotrexate (MTX) on the density of CC chemokine receptor 2 (CCR2) and CXC chemokine receptor 3 (CXCR3) on circulating monocytes, and the coexpression of CXCR3 and CCR2 on CD4 T lymphocytes in patients with active chronic rheumatoid arthritis. METHODS: All 34 patients with rheumatoid arthritis fulfilled the 1987 American Rheumatism Association criteria and were followed for 16 weeks after starting MTX. Peripheral blood mononuclear cells were analysed for CCR2 and CXCR3 density by three-colour flow cytometry before initiation of MTX and at week 12. RESULTS: 22 (65%) patients were non-responders, 12 (35%) patients responded to MTX by American College of Rheumatology (ACR)20% criteria, and 8 (24%) of these patients responded by ACR50%. In patients with active rheumatoid arthritis before starting MTX, CCR2 density on circulating monocytes, CD4(+) CXCR3(+) and CD4(+) CXCR3(-) T lymphocytes was increased compared with controls. During 12 weeks of MTX treatment, the CCR2 density on monocytes decreased significantly in the ACR50% group but not in the ACR20% and non-responder groups. The increased CCR2 density on CD4(+) CXCR3(+) and CD4(+) CXCR3(-) T lymphocytes was unaffected by the reduction in disease activity measured in relation to MTX treatment. The percentage of both monocytes and CD4(+) CXCR3(+) and CD4+ CXCR3(-) T lymphocytes among the peripheral circulating mononuclear cells did not change during MTX treatment. CONCLUSIONS: Active chronic rheumatoid arthritis is characterised by enhanced CCR2 density on circulating monocytes and CD4(+) CXCR3(+) and CD4(+) CXCR3(-) T lymphocytes. During MTX treatment, a decrease in CCR2 density on monocytes in the ACR50% responder group was associated with decreased disease activity. The increased CCR2 density on CD4(+) CXCR3(+) and CD4(+) CXCR3(-) T lymphocytes was uninfluenced by MTX and disease activity.
17985419 Optimizing treatment with biologics. 2007 Nov Disability and joint damage in rheumatoid arthritis (RA) occur rapidly and early in the course of the disease. Disease activity is predominantly responsible for the disability in the early stages of RA. Nonreversible joint damage increases disability later in the course of RA. In recent years, several strategies that employed combination therapies with conventional disease modifying antirheumatic drugs (DMARD) were studied with the aim of rapidly bringing the disease under control. The ultimate goal was to alleviate symptoms and slow or halt the progression of joint damage. The introduction of highly efficient biologic agents allows introduction of a number of new strategies, including early administration of a biologic agent alone or in combination with high-dose methotrexate. Other options for the use of biologic therapies include the use of biologic agents for moderate disease, and early use of a biologic agent for induction of remission and subsequent treatment with a conventional DMARD. A strategy for tight control of disease with targeted outcomes for decision-making may offer further improvement in disease control irrespective of the treatment approach. The remarkably improved outcomes that can be achieved by initiating aggressive therapy early, with close monitoring of disease progression and modification of ineffective therapeutic strategies, support the use of biologics in the optimal management of RA.
17129076 Cost effectiveness of tumour necrosis factor-alpha inhibitors as first-line agents in rheu 2006 BACKGROUND AND OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease with an unknown aetiology that results in >9 million physician visits and >250 000 hospitalisations per year in the US. Tumour necrosis factor-alpha (TNFalpha) inhibitors are effective agents in treating RA; however, their cost effectiveness as first-line agents has not been investigated. This study aimed to examine the cost effectiveness of using TNFalpha inhibitors (both as monotherapy and in combination with methotrexate) as first-line agents versus methotrexate (monotherapy) from a payer perspective. METHODS: A Markov model was developed utilising a discount rate of 3% per annum, a cycle length of 1 year and a lifetime time-horizon for a hypothetical cohort of US females aged 55-60 years who had been diagnosed with RA. The source of data for predicted probabilities, expected mortality rates and treatment costs in year 2005 US dollars (drug, toxicity, monitoring and hospitalisation) was from the literature. These costs are assigned in 5-year cycles (calculated from initial 1-year estimates) along with the effect on quality-adjusted life-years (QALYs), which were calculated using the Health Assessment Questionnaire score. Univariate sensitivity analyses were conducted on all relevant parameters. RESULTS: Adalimumab, etanercept, adalimumab plus methotrexate and infliximab plus methotrexate had incremental cost-effectiveness ratios (ICERs) versus methotrexate monotherapy of $US63 769, $US89 772, $US194 589 and $US409 523 per QALY, respectively. When taking into consideration age at diagnosis, the ICER for etanercept ranged from $US84 129 to $US96 225 per QALY. In considering males for the base-case age at diagnosis, the ICER for etanercept versus methotrexate was $US85 100 per QALY. The average lifetime cost across all treatment arms in a woman diagnosed between 55 and 60 years of age was $US211 702. CONCLUSION: While these ICERs cannot be used to directly compare one biological agent with another since there are no comparative trials, they do provide a valid comparison versus methotrexate as first-line agents. Depending where the cost-effectiveness threshold is drawn (i.e. whether it is considered to be $US50 000 or $US100 000 per QALY), etanercept and adalimumab may be considered relatively cost-effective first-line treatments for RA compared with methotrexate monotherapy.
19066176 Golimumab, a human antibody to tumour necrosis factor {alpha} given by monthly subcutaneou 2009 Jun OBJECTIVE: The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate therapy. METHODS: Patients were randomly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules (group 1, n = 133), golimumab 100 mg injections plus placebo capsules (group 2, n = 133), golimumab 50 mg injections plus methotrexate capsules (group 3, n = 89), or golimumab 100 mg injections plus methotrexate capsules (group 4, n = 89). Injections were administered subcutaneously every 4 weeks. The co-primary endpoints were the proportion of patients with 20% or greater improvement in the American College of Rheumatology criteria (ACR20) at week 14 and the change from baseline in the health assessment questionnaire-disability index (HAQ-DI) score at week 24. RESULTS: The proportion of patients who achieved an ACR20 response at week 14 was 33.1% in the placebo plus methotrexate group, 44.4% (p = 0.059) in the golimumab 100 mg plus placebo group, 55.1% (p = 0.001) in the golimumab 50 mg plus methotrexate group and 56.2% (p<0.001) in the golimumab 100 mg plus methotrexate group. At week 24, median improvements from baseline in HAQ-DI scores were 0.13, 0.13 (p = 0.240), 0.38 (p<0.001) and 0.50 (p<0.001), respectively. During the placebo-controlled portion of the study (to week 16), serious adverse events occurred in 2.3%, 3.8%, 5.6% and 9.0% of patients and serious infections occurred in 0.8%, 0.8%, 2.2% and 5.6%, respectively. CONCLUSION: The addition of golimumab to methotrexate in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function.
17929132 Methotrexate reduces the levels of pentosidine and 8-hydroxy-deoxy guanosine in patients w 2007 This study was performed to investigate whether methotrexate (MTX) affects the levels of oxidative stress markers, including pentosidine one of the glycation end products (AGEs) or 8-hydroxy-deoxy guanosine (8-OHdG). These stress markers represent DNA damage; 19 rheumatoid arthritis (RA) patients underwent MTX treatment. The levels of serum total, urinary total, urinary-free pentosidine and also urinary 8-OHdG, as well as clinical parameters, including disease activity scores for 28 joints (DAS28) were measured at baseline and at 3 and 6 months after the initial treatment with MTX. After the initial treatment with MTX, serum total and urinary total pentosidine levels were reduced at 6 months, and urinary-free pentosidine levels were reduced at 3 and 6 months. Urinary 8-OHdG levels also were significantly reduced at 6 months after the initial treatment with MTX. This study demonstrated that MTX plays a role as a regulator against pentosidine formation and oxidative DNA damage in RA patients.
16583484 Mycobacterium marinum arthritis mimicking rheumatoid arthritis. 2006 Apr Mycobacterium marinum is an atypical mycobacterium found in salt and fresh water. M. marinum infection occurs following skin trauma in fresh or salt water and usually presents as a localized granuloma or sporotrichotic lymphangitis. It rarely affects the musculoskeletal system. We describe a patient who presented with subcutaneous nodules and an inflammatory arthritis that was thought to be rheumatoid arthritis, and was treated as such with corticosteroids, methotrexate, and anti-tumor necrosis factor-alpha therapy, with worsening of his arthritis.
18812430 Variation of immunological response in methotrexate-induced pneumonitis. 2008 Nov OBJECTIVES: To assess the variation of peripheral blood and bronchoalveolar lavage (BAL) inflammatory cell counts and lung biopsy findings with the degree of exposure to MTX therapy. METHODS: Fifty-six (16 males; 40 females) reported cases of MTX-induced pneumonitis (MTX-P) on low-dose MTX (5-30 mg) were identified from a literature search and classified using Searles and McKendry's criteria. The median cumulative dose was 300 mg and this was used to categorize patients into low and high MTX-exposure groups and 6 months was used to divide patients into early- and late-onset MTX-P groups. RESULTS: Neutrophil counts in the peripheral blood and BAL were significantly raised in the low MTX-exposure group compared with the high MTX-exposure group (P = 0.018 and 0.038, respectively). There were similar findings when early-onset was compared with late-onset group. Lymphocytes in BAL were significantly higher in the high MTX-exposure group compared with low-dose cumulative group (P = 0.007). There were 6 (11%) recorded deaths and all were in the low MTX-exposure group. Early-onset/low MTX-exposure groups had a high prevalence of lung fibrosis. CONCLUSIONS: This is the first study to describe the variation of immunological responses in MTX-P with the degree of exposure to MTX. Our findings suggest that MTX-P can be divided into two groups: type 1 MTX-P that occurs early, predominated by neutrophils, lung fibrosis and has a high mortality; and type 2 MTX-P that occurs late, predominated by lymphocytes, has less lung fibrosis and low mortality.
16761535 Placental umbilical cord whole blood transfusion to combat anemia in the background of adv 2006 Rheumatoid arthritis is the commonest form of inflammatory arthritis and affects about 1-3% of the population in the West and even more in the developing world due to the compounded factors of late detection and inadequate treatment in the overall background of poverty, deprivation, and improper macro and micronutrients in the diet in a sizeable segment of the population. Nearly 90% of patients with aggressive disease will become clinically disabled within 20 years. Furthermore, in patients with severe disease or extra-articular symptoms, mortality is equal to that for patients with triple artery coronary artery disease or Stage IV Hodgkin's lymphoma. Anemia is a very common comorbidity of rheumatoid arthritis. Anemia in rheumatoid arthritis is caused by various factors, for instance, cytokine impact of the advanced arthritic process on the host, or lack of proper nutrition and essential micronutrients in the diet, or coexistent helminthiasis, and/or impact of antiarthritic drugs on the host system, i.e., high steroid induced gastritis or ulcerations in gastric mucosa or subclinical or clinical hepatitis due to methotrexate or salazopyrin effects on bone marrow, only to name a few. Other pre-existing or compounding gastrointestinal problems, which alter the available iron stores or cause bone marrow dysfunction, may also help in adding to an anemic condition. If the anemia is 8 g/dl or less, blood transfusion or erythropoietin injection with adequate hematinic reserve is effective in normal situations, but is not that effective in anemia with a chronic disease background like rheumatoid arthritis. Cord blood, because of its rich mix of fetal and adult hemoglobin, high platelet and white blood cell (WBC) counts, and a plasma filled with cytokine and growth factors, as well as its hypo antigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood transfusion. Seventy-eight units (42 ml -136 ml mean 80.6 ml +/- 3.6 ml SD, median 82.4 ml, mean packed cell volume 48.2 +/- 2.1 SD, mean percent hemoglobin concentration 16.4 g/dl +/- 1.5 g/dl SD) of placental umbilical cord whole blood was transfused (from 1 April 1999 to April 2005) after lower uterine cesarean section (LUCS) from consenting mothers to 28 informed consenting patients with advanced rheumatoid arthritis who had plasma hemoglobin of 8 g/dl or less. After collection, the blood was immediately transfused following the standard adult blood transfusion protocol. Each case was passed through the institutional ethical committee. The patients received two to six units of freshly collected placental umbilical cord blood without encountering any clinical, immunological or non-immunological reactions. Three days after completion of the transfusion of placental umbilical cord blood, the peripheral blood hematopoietic stem cell (CD34) estimation revealed a rise from the pretransfusion base level (.09%), varying from 2.03 to 23%, which returned to base level in most of the cases at the three-month CD34 re-estimation, without provoking any clinical graft vs host reaction in any of the patients.
19015207 Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis 2009 Jun BACKGROUND: Certolizumab pegol is a PEGylated tumour necrosis factor inhibitor. OBJECTIVE: To evaluate the efficacy and safety of certolizumab pegol versus placebo, plus methotrexate (MTX), in patients with active rheumatoid arthritis (RA). METHODS: An international, multicentre, phase 3, randomised, double-blind, placebo-controlled study in active adult-onset RA. Patients (n = 619) were randomised 2:2:1 to subcutaneous certolizumab pegol (liquid formulation) 400 mg at weeks 0, 2 and 4 followed by 200 mg or 400 mg plus MTX, or placebo plus MTX, every 2 weeks for 24 weeks. The primary end point was ACR20 response at week 24. Secondary end points included ACR50 and ACR70 responses, change from baseline in modified Total Sharp Score, ACR core set variables and physical function. RESULTS: Significantly more patients in the certolizumab pegol 200 mg and 400 mg groups achieved an ACR20 response versus placebo (p< or =0.001); rates were 57.3%, 57.6% and 8.7%, respectively. Certolizumab pegol 200 and 400 mg also significantly inhibited radiographic progression; mean changes from baseline in mTSS at week 24 were 0.2 and -0.4, respectively, versus 1.2 for placebo (rank analysis p< or =0.01). Certolizumab pegol-treated patients reported rapid and significant improvements in physical function versus placebo; mean changes from baseline in HAQ-DI at week 24 were -0.50 and -0.50, respectively, versus -0.14 for placebo (p< or =0.001). Most adverse events were mild or moderate, with low incidence of withdrawals due to adverse events. Five patients developed tuberculosis. CONCLUSION: Certolizumab pegol plus MTX was more efficacious than placebo plus MTX, rapidly and significantly improving signs and symptoms of RA and physical function and inhibiting radiographic progression. TRIAL REGISTRATION NUMBER: NCT00175877.
17787045 Infliximab but not methotrexate induces extra-high levels of VLDL-triglyceride in patients 2007 Oct OBJECTIVE: Tumor necrosis factor (TNF-alpha), a pivotal inflammatory cytokine, is known to induce proatherogenic changes in the lipid profile and may increase the cardiovascular risk of patients with rheumatoid arthritis (RA). We examined the effects of anti-TNF-alpha antibody (infliximab, IFX) compared with methotrexate (MTX) on lipid profiles in patients with RA. METHODS: We selected retrospectively all patients with refractory RA (n = 32) who achieved a successful outcome (DAS-28 score < 2.6) in 6 months with IFX treatment, and control groups of age- and sex-matched patients with active RA treated with MTX and healthy participants. We traced fasting serum levels of total cholesterol (TCHO) and triglyceride (TG) for 6 months and used an online dual enzymatic method for simultaneous quantification of cholesterol (CHO) and TG by high performance liquid chromatography (HPLC). RESULTS: Mean C-reactive protein levels (baseline 4.5) fell to below 1 in 6 months. MTX treatment elevated and normalized TCHO and TG levels. IFX treatment, however, preferentially induced extra-high TG levels. HPLC analyses identified similar CHO profiles between patients treated with IFX or MTX, but IFX selectively induced a huge VLDL-TG peak. Statins successfully controlled these extra-high TG levels. CONCLUSION: In patients successfully treated with IFX or MTX, CHO levels were elevated and normalized, but IFX treatment preferentially induced extra-high levels of VLDL-TG. Thus, there is differential regulation of the lipid profile between IFX and MTX, necessitating careful attention to TG levels with IFX treatment.
17114190 A randomised, double-blind, placebo-controlled trial of a recombinant version of human alp 2007 May BACKGROUND: Rheumatoid arthritis (RA) tends to remit during pregnancy, with more patients achieving remission in the third trimester, coinciding with an increase in levels of alpha-fetoprotein (AFP). In vitro and animal studies have shown that AFP has immunomodulatory properties. MM-093 is a non-glycosylated, recombinant version of human AFP. OBJECTIVE: To assess the safety, tolerability and clinical effects of MM-093 during a 12-week, randomised, double-blind, placebo-controlled study. METHODS: 12 patients with RA, who had active disease and were on stable doses of methotrexate, received weekly subcutaneous injections of placebo or 21 mg of MM-093. Assessments were carried out at baseline and weekly thereafter. RESULTS: Baseline characteristics were similar in both groups. There was one dropout in the placebo group, due to flare of disease. Treatment with MM-093 was well tolerated. No serious adverse event was observed. By day 85, MM-093 produced a significant mean improvement from baseline in Disease Activity Score 28 (DAS28; 0.913 vs 0.008, p = 0.033) and patient's global assessment (28.9% vs -36.3%, p = 0.02) compared with placebo. CONCLUSION: This is the first randomised, controlled trial of MM-093, a recombinant version of human AFP, in patients with RA. MM-093 was well tolerated. Evidence of efficacy was observed, suggesting that MM-093 may have therapeutic potential in RA.
16267598 The incidence of Proteus mirabilis infection increases in patients on treatment but does n 2006 Jul The aim of this study is to determine whether treatment increases the levels of anti-Proteus antibodies (APA) in patients with rheumatoid arthritis (RA). The blood samples of 32 patients suffering from RA who were recruited in our previous study and continued to participate in our follow-up study were collected after 1 year. Their first and follow-up samples were analysed for the presence of IgG isotype and total immunoglobulins (IgG+IgA+IgM) against Proteus mirabalis (PM) using enzyme-linked immunosorbent assay with two kinds of antigen preparations: whole bacteria and sodium dodecyl sulphate (SDS) lysed bacterial extract. All patients were treated with methotrexate and hydroxychloroquine with adequate dose of non-steroidal anti-inflammatory drug. After 1 year, 11 patients were in clinical remission [erythrocyte sedimentation rate (ESR) less than 30 mm/h and C-reactive protein (CRP) less than or equal to 10 mg/l], while the rest of the 21 were in the state of active disease. Correlation and Student's t test were used for statistical analysis. APA titres were significantly elevated in patients after 1 year of therapy. However, the rise was not different between patients who were in clinical remission and those in the state of active disease. APA titre increases in the treatment of RA, and the probable mechanisms are discussed.
16760833 [Cutaneous vasculitis with necrotic ulcers in rheumatoid arthritis: treatment with anti-TN 2006 May INTRODUCTION: Anti-TNFalpha has occasionally been used in the treatment of recalcitrant forms of systemic vasculitis such as Behçet's disease, Wegener's granulomatosis and Churg-Strauss syndrome. We report on the outcome of treatment in rheumatoid arthritis patients with cutaneous vasculitis lesions on anti-TNFalpha. OBSERVATIONS: Two patients with rheumatoid arthritis present for several years had necrotic ulcers of the lower limbs due to cutaneous vasculitis. After the failure of various immunosuppressive drugs (cyclophosphamide, azathioprine, methotrexate), the two patients were treated with anti-TNFalpha: infliximab in the first case and adalimumab in the second. Cutaneous ulcers healed within two to four months of the start of anti-TNFalpha treatment. Despite ongoing anti-TNFalpha treatment, these cutaneous ulcers relapsed four to six months after complete healing. CONCLUSION: Initially spectacular healing of cutaneous vasculitis ulcers under anti-TNF alpha treatment followed by relapse after several months of treatment is suggestive of an escape mechanism.
18830904 Modulatory effects of inflammation and therapy on GDF-5 expression in rheumatoid arthritis 2008 Nov OBJECTIVE: Growth differentiation factor-5 (GDF-5), a member of the transforming growth factor (TGF)-beta family, is involved in joint development during embryogenesis and has the potential to regenerate cartilage in adult animals. As progression of chronic joint diseases is influenced by cytokines of the synovial tissue, we examined the expression and effects of GDF-5 in this tissue. METHODS: Microarray experiments were investigated for differential expression of GDF-5 in synovial tissues, synovial fibroblasts, and peripheral blood cells. GDF-5 expression was validated by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry, double immunofluorescence, and in situ hybridization in synovial tissue of normal donors (ND) and patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Effects of inflammation and therapy were investigated in RA and OA fibroblasts after stimulation with interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, methotrexate (MTX), and prednisolone. The influence of GDF-5 on macrophages was studied by chemotaxis assay. RESULTS: Microarray analysis and immunostaining revealed expression predominantly in synovial fibroblasts. Compared to patients without immunomodulating drugs, expression of GDF-5 was decreased significantly in patients receiving glucocorticoids and/or disease-modifying antirheumatic drugs (DMARDs) (p = 0.007), but did not differ between the total group of ND, OA, and RA. Stimulation with prednisolone and TNFalpha reduced GDF-5 expression in OA and RA fibroblasts, whereas MTX and IL-1beta revealed minor or no relevant change. GDF-5 also reduced cell migration of macrophages (p<0.001). CONCLUSION: GDF-5 is expressed in synovial fibroblasts and may counteract macrophage infiltration. Its modulation by inflammation and therapy suggests that glucocorticoids play a conflicting role by suppressing not only inflammation but also putative mechanisms of repair.
16570441 [Clinical observation on treatment of rheumatoid arthritis with cake-separated mild moxibu 2006 Mar OBJECTIVE: To observe the effect-increasing action of cake-separated mild moxibustion on rheumatoid arthritis (RA), and to probe a new method for RA. METHODS: Sixty cases were randomly divided into 2 groups. The control group (n=30) were treated with oral administration of methotrexate (MTX) as basic treatment, and non-steroid anti-inflammatory agents (NSAIDs) according to conditions of the patient. The treatment group (n=30) were treated with the same treatment as the control group, and Fuzi case-separated moxibustion at Guanyuan (CV 4) and Zusanli (ST 36) was added. They were treated for 3 months. RESULTS: After treatment of 3 months, the total effective rate was 83.3% in the treatment group, which was higher than 60.0% in the control group (P < 0.05); there were significant differences before and after treatment in all indexes in the two groups (P < 0.05 or P < 0.01); the ratio of the patients who completely withdrew NSAIDs in the treatment group was significantly higher than that in the control group (P < 0.05); the rate of adverse reaction in the treatment group was significantly lower than that in the control group (P < 0.05). CONCLUSION: Fuzi cake-separated mild moxibustion can increase clinical therapeutic effect on RA and reduce dosage of NSAIDs.